Computational modeling of retinal hypoxia and photoreceptor degeneration in patients with age-related macular degeneration.

Although drusen have long been acknowledged as a primary hallmark of dry age-related macular degeneration (AMD) their role in the disease remains unclear. We hypothesize that drusen accumulation increases the barrier to metabolite transport ultimately resulting in photoreceptor cell death. To investigate this hypothesis, a computational model was developed to evaluate steady-state oxygen distribution in the retina. Optical coherence tomography images from fifteen AMD patients and six control subjects were segmented and translated into 3D in silico representations of retinal morphology. A finite element model was then used to determine the steady-state oxygen distribution throughout the retina for both generic and patient-specific retinal morphology. Oxygen levels were compared to the change in retinal thickness at a later time point to observe possible correlations. The generic finite element model of oxygen concentration in the retina agreed closely with both experimental measurements from literature and clinical observations, including the minimal pathological drusen size identified by AREDS (64 μm). Modeling oxygen distribution in the outer retina of AMD patients showed a substantially stronger correlation between hypoxia and future retinal thinning (Pearson correlation coefficient, r = 0.2162) than between drusen height and retinal thinning (r = 0.0303) indicating the potential value of this physiology-based approach. This study presents proof-of-concept for the potential utility of finite element modeling in evaluating retinal health and also suggests a potential link between transport and AMD pathogenesis. This strategy may prove useful as a prognostic tool for predicting the clinical risk of AMD progression.

Déclaration de conflit d'intérêts

K.M., M.S.G., and L.A.K. hold a patent (US9986905B2) entitled “Predicting retinal degeneration based on three-dimensional modeling of oxygen concentration.” This patent outlines the technique used here to assess steady-state retinal oxygen levels in the retina using OCT images and finite element analysis. S.F. holds several patents (US9299155B2, US8811745B2, US20110182517A1, and US20120184846A1), which relate to the segmentation method used to identify retinal layers in OCT images. This does not alter our adherence to PLOS ONE policies on sharing data and materials.